Toxicology of baclofen continuously infused into the spinal intrathecal space of the dog

M. B. Sabbe, Marjorie Grafe, B. L. Pfeifer, T. H M Mirzai, T. L. Yaksh

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The continuous spinal administration of baclofen has been shown to have therapeutic benefit in the management of spasticity in humans with neuraxial injuries. The present study systematically investigated the potential spinal neurotoxicity of continuous intrathecally-infused baclofen in dogs. Male beagle dogs were prepared with chronic lumbar intrathecal catheters connected to subcutaneously implanted infusion pumps. Three groups of dogs received 28 days of infusion of saline (vehicle: 1 ml/24 hrs; N = 10), 200 μg/ml/24 hrs baclofen (N = 10) or 2000 μg/ml/24 hrs baclofen (N = 10). A mild, dose- dependent anti-nociception and muscle weakness was observed. Independent assessment of spinal histopathology in dogs sacrificed and perfusion fixed at 28 days of treatment revealed a mild fibrotic reaction to the catheter, but there were no changes distinguishable from vehicle infused animals which could be ascribed to any dose of intrathecal baclofen. Cisternal CSF protein and cells in samples taken at sacrifice were also not different for the three groups. These findings with chronic intrathecally administered baclofen in this dog model jointly support the lack of toxicity of chronic intrathecal baclofen at concentrations up to 2000 μg/ml.

Original languageEnglish (US)
Pages (from-to)397-410
Number of pages14
JournalNeuroToxicology
Volume14
Issue number4
StatePublished - 1993
Externally publishedYes

Fingerprint

Baclofen
Toxicology
Dogs
Catheters
Infusion Pumps
Nociception
Muscle Weakness
Toxicity
Muscle
Animals
Perfusion
Pumps
Wounds and Injuries

Keywords

  • Antinociception
  • Baclofen
  • Intrathecal Drug
  • Neurotoxicity
  • Spasticity
  • Spinal Cord

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience
  • Toxicology

Cite this

Sabbe, M. B., Grafe, M., Pfeifer, B. L., Mirzai, T. H. M., & Yaksh, T. L. (1993). Toxicology of baclofen continuously infused into the spinal intrathecal space of the dog. NeuroToxicology, 14(4), 397-410.

Toxicology of baclofen continuously infused into the spinal intrathecal space of the dog. / Sabbe, M. B.; Grafe, Marjorie; Pfeifer, B. L.; Mirzai, T. H M; Yaksh, T. L.

In: NeuroToxicology, Vol. 14, No. 4, 1993, p. 397-410.

Research output: Contribution to journalArticle

Sabbe, MB, Grafe, M, Pfeifer, BL, Mirzai, THM & Yaksh, TL 1993, 'Toxicology of baclofen continuously infused into the spinal intrathecal space of the dog', NeuroToxicology, vol. 14, no. 4, pp. 397-410.
Sabbe, M. B. ; Grafe, Marjorie ; Pfeifer, B. L. ; Mirzai, T. H M ; Yaksh, T. L. / Toxicology of baclofen continuously infused into the spinal intrathecal space of the dog. In: NeuroToxicology. 1993 ; Vol. 14, No. 4. pp. 397-410.
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